Project Summary/Abstract This proposal requests funds to purchase a Seahorse XFe96 Analyzer (Agilent Technologies) at the University of Mississippi (Oxford, MS). The Seahorse Analyzer produces rapid and reliable quantitative information on mitochondrial function (via respiration) and glycolysis (via acidification), the primary pathways involved in ATP production. The analyzer can assess oxidative phosphorylation, ATP production, proton efflux, glycolysis, and glycolytic capacity in small sample volumes (~2 ?L). There is currently no instrument available on the Oxford campus with these capabilities. The proposed Seahorse analyzer will be housed as part of our COBRE- supported Center of Research Excellence in Natural Products Neuroscience (CORE-NPN) Pharmacology Core. A cross-disciplinary consortium of highly-productive researchers from the Departments of BioMolecular Sciences (Divisions of Pharmacology, Pharmacognosy, and Environmental Toxicology), Chemistry & Biochemistry, Biology, and the National Center for Natural Products Research will serve as initial users of the Seahorse Analyzer (80% user time is dedicated to current NIH-funded projects). The Major Users will include: the PI, Jason Paris (neurodegeneration, virology: interactions between drugs of abuse and neuroAIDS), Yu-Dong Zhou (cancer, tumor physiology: drug discovery to identify novel antimetastatic compounds), Kristine Willett (neurodegeneration, development, cancer: cannabinoid and environmental toxin exposure in marine life), James Stewart (diabetes, obesity, cardiovascular function: cardiovascular dysfunction in the obese or diabetic heart), and Nicole Ashpole (aging, neurodegeneration: age-related neurodegeneration and cognitive-decline). Minor Users include Mika Jekabsons (cancer, metabolomics), Ameeta Agarwal (antifungal drug discovery, metabolomics), Dale G. Nagle (herbal supplement pharmacology, antitumor drug discovery), Marc Slattery and Deborah Gochfeld (marine-based drug discovery), Ziaeddin Shariat-Madar (cardiovascular function, mitochondrial physiology), Joshua Bloomekatz (pediatric cardiomyopathy) and Cole Stevens (myxobacterial drug discovery). Investigators are in adjacent buildings, have a history of collaboration, and conduct translational research across a range of models from human and rodent tissues to zebrafish, sea sponges, fungi, and bacteria. The University is committed to support the Seahorse analyzer. An internal advisory committee will provide instrument oversight, help direct the PI's business plan, and maintain the service contract. The PI will generate usage statistics for compliance and maintain the analyzer along with the Instrument Manager (Fakhri Mahdi). Preliminary data demonstrate the improved accuracy and efficiency of the Seahorse over current instrumentation, as well as additional bioenergetics measures that cannot be attained in small or primary samples using other techniques. If awarded, this platform will be the only Seahorse analyzer within 243 miles driving a strong user-base evidenced by letters of support from nearby institutions. This equipment will catalyze basic and translational bioenergetics/metabolomics research within the University of Mississippi and the region.